What empiric antibiotic regimen and duration should be used for a critically ill adult with a suspected hospital‑acquired multidrug‑resistant Acinetobacter nosocomialis infection?

Empiric Treatment of Suspected Multidrug-Resistant Acinetobacter nosocomialis in Critically Ill Adults

For a critically ill adult with suspected hospital-acquired multidrug-resistant Acinetobacter nosocomialis infection, initiate empiric broad-spectrum combination therapy with a carbapenem (imipenem, meropenem, or doripenem) plus either colistin or ampicillin-sulbactam, targeting the infection for 14 days, with de-escalation based on culture results at 72 hours. 1

Initial Empiric Regimen Selection

Start combination therapy immediately in critically ill patients with septic shock or high-risk features. The most effective empiric agents for Acinetobacter species are carbapenems, sulbactam, colistin, and polymyxin B. 2 Since A. nosocomialis is part of the A. baumannii complex, it should be managed identically to A. baumannii infections, as routine clinical laboratories need not distinguish between species for treatment purposes. 3, 1

High-Risk Criteria Requiring Empiric Coverage

Empiric coverage is warranted when patients present with:

• Severe sepsis or septic shock 2, 1
• Active Acinetobacter outbreak in the ICU 1
• Previous colonization with multidrug-resistant Acinetobacter 1
• Recent broad-spectrum antibiotic exposure 1
• Prolonged hospitalization (>5 days) 2
• Settings with >25% prevalence of resistant pathogens in local surveillance data 2

Specific Antibiotic Regimens

First-Line Empiric Combination Therapy

Carbapenem-based regimen:

• Imipenem, meropenem, or doripenem at full doses 2, 1, 4, 5
• PLUS colistin: Loading dose of 9 million IU, then 4.5 million IU every 12 hours (adjusted for renal function) 1
• OR ampicillin-sulbactam: 3-16 g every 8 hours 1

The carbapenems remain the mainstay of treatment for Acinetobacter infections and are the most consistently effective antibiotics. 2, 5 Combination therapy is recommended for critically ill patients to ensure at least one active agent is included and to reduce the risk of inappropriate therapy. 2, 1

Alternative for Carbapenem-Resistant Isolates

If local epidemiology suggests high carbapenem resistance or the patient has risk factors for carbapenem-resistant Acinetobacter:

• Ampicillin-sulbactam is preferred over polymyxins for sulbactam-susceptible infections based on superior mortality outcomes 3, 1
• Intravenous polymyxins (colistin or polymyxin B) for infections resistant to both carbapenems and sulbactam 3, 1

Obtaining Cultures Before Treatment

Obtain lower respiratory tract samples (distal quantitative or proximal quantitative cultures) and blood cultures before initiating antibiotics, but do not delay treatment in critically ill patients. 2, 3 These samples are essential to focus and narrow the initial empiric therapy once susceptibility data become available. 2

De-escalation Strategy at 72 Hours

Transition to monotherapy with a single active agent once culture results and susceptibilities are available, unless the patient remains in septic shock or at high risk for death. 1 This represents good clinical practice and reduces unnecessary antibiotic exposure. 2

• If cultures grow carbapenem-susceptible Acinetobacter: Continue carbapenem monotherapy 1
• If cultures grow carbapenem-resistant but sulbactam-susceptible Acinetobacter: Switch to ampicillin-sulbactam monotherapy 3, 1
• If cultures grow carbapenem-resistant and sulbactam-resistant Acinetobacter: Continue polymyxin therapy 3, 1
• If cultures are negative and clinical improvement occurs: Consider stopping Acinetobacter coverage 2

Treatment Duration

Continue antimicrobial therapy for 14 days for bacteremia or severe infections, especially in cases manifesting as severe sepsis or septic shock. 3 For ventilator-associated pneumonia specifically caused by Acinetobacter, a 7-day course is recommended. 1

Critical Monitoring Requirements

Monitor renal function closely throughout therapy, as nephrotoxicity occurs in up to 53.7% of patients receiving colistin. 3, 1 Polymyxin B appears to cause less nephrotoxicity than colistin. 1 Monitor for clinical response and consider repeat blood cultures to document clearance. 3

Infection Control Measures

Implement strict contact precautions immediately upon suspicion or identification of Acinetobacter infection. 3, 1 Additional measures include:

• Alert systems to identify the patient promptly if readmitted 3
• Thorough environmental cleaning with hypochlorite solutions (0.5%) 3
• Surveillance cultures in outbreak settings 1
• Antibiotic stewardship programs to control resistance emergence 3, 1

Critical Pitfalls to Avoid

Never use the following approaches:

• Ertapenem (lacks activity against Acinetobacter) 1
• Aminoglycoside monotherapy for serious infections 3
• Tigecycline monotherapy for bacteremia due to suboptimal serum concentrations 3
• Omitting loading doses of colistin 1
• Assuming carbapenem susceptibility in endemic areas or during outbreaks without testing 3, 1
• Delaying empirical coverage in previously colonized patients presenting with severe sepsis 3, 1

Special Considerations

Be aware that colistin heteroresistance occurs in 18.7-100% of isolates, with previous colistin use as a risk factor. 1 The rate of resistant pathogens varies widely across different countries, settings, and hospitals, so knowledge of local susceptibility patterns is essential to guide empirical therapy. 5 The ICU-specific resistance rate (not the hospital as a whole) is the relevant factor to consider. 2